IgG from Adult Atopic Dermatitis (AD) Patients Induces Nonatopic Neonatal Thymic Gamma-Delta T Cells (gamma delta T) to Acquire IL-22/IL-17 Secretion Profile with Skin-Homing Properties and Epigenetic Implications Mediated by miRNA

Author(s)

Fagundes, Beatriz Oliveira ; de Sousa, Thamires Rodrigues ; Nascimento, Andrezza ; Fernandes, Lorena Abreu ; Sgnotto, Fabio da Ressureicao ; Orfali, Raquel Leao ; Aoki, Valeria ; Duarte, Alberto Jose da Silva ; Sanabani, Sabri Saeed ; Victor, Jefferson Russo

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 12, p. 16-pg., 2022-06-01.

Abstract

gamma delta T cells mature in the human thymus, and mainly produce IL-17A or IFN-gamma, but can also produce IL-22 and modulate a variety of immune responses. Here, we aimed to evaluate whether IgG from AD patients (AD IgG) can functionally modulate thymic nonatopic gamma delta T cells. Thymic tissues were obtained from 12 infants who had not had an atopic history. Thymocytes were cultured in mock condition, or in the presence of either AD IgG or therapeutic intravenous IgG (IVIg). Following these treatments, intracellular cytokine production, phenotype, and microRNA expression profiles were investigated. AD IgG could downregulate alpha 4 beta 7, upregulate CLA, and induce the production of IFN-gamma, IL-17, and IL-22 in gamma delta T cells. Although both AD IgG and IVIg could directly interact with gamma delta T cell membranes, AD IgG could reduce gamma delta T cell apoptosis. AD IgG could upregulate nine miRNAs compared to IVIg, and six when compared to the mock condition. In parallel, some miRNAs were downregulated. Target gene prediction and functional analysis indicated that some target genes were enriched in the negative regulation of cellular transcription. This study shows that AD IgG influences the production of IL-17 and IL-22 by intrathymic nonatopic gamma delta T cells, and demonstrates epigenetic implications mediated by miRNAs. (AU)

• FAPESP's process: 18/05181-7 - Translational evaluation of IgG effect upon the maturation of offspring thymus derived TCD4, TCD8, nTreg, gammadeltaT and e B cells.
• Grantee: Alberto José da Silva Duarte
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/08631-3 - Bacterial Community Composition and Diversity in Billing Reservoir Examined by Massive Paralelel Sequence Analysis of 16S rRNA Genes
• Grantee: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/09741-0 - Analysis of the modulating effect of IgG antibodies from atopic individuals to the mite Dermatophagoides pteronyssiunus on the maturation and cytokine production of human intrathymic lymphocytes
• Grantee: Thamires Rodrigues de Sousa
• Support Opportunities: Scholarships in Brazil - Scientific Initiation